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Sunday, May 4, 2008

The reason fat people find it hard to lose weight is found

Scientists have discovered why fat people find it so hard to lose weight, which will lead to many new approaches to weight loss.The difference in the number of fat cells between lean and obese people is established in childhood and, although fat people replenish fat cells at the same rate as thin ones, they have around twice as many.

This remarkable glimpse of what gives us beer guts, love handle and muffin tops could also lead to new approaches to fight the flab, by cutting the overall number of fat cells in the body, as well as providing an insight into why fat people find it so hard to lose weight, because the number of fat cells in a person remains the same, even after a successful diet.

The details of how humans regulate their fat mass is reported today in the journal Nature by a team led by scientists at the Karlolinksa Institute, Stockholm, Sweden, as a second team, led by Imperial College London, reports in the journal Nature Genetics the discovery of a gene sequence present in half the population linked to three quarters of an inch bigger waistline, four lb gain in weight, and a tendency to become resistant to insulin, which can lead to type 2 diabetes.

The fundamental new insight into the cause of obesity comes from an international team lead by Dr Kirsty Spalding, Prof Jonas Frisén and Prof Peter Arner who found the body constantly produces new fat cells to replace equally rapid break down of the already existing fat cells due to cell death.

They also show, that overweight people generate and replace more fat cells than do lean - and that the total number of fat cells stays equal after a diet program.

Until now, it was not clear that adults could make new fat cells. Some had assumed that they increase their fat mass by incorporating more fats into already existing fat cells in order to maintain their body weight (lean, overweight, obese). However now it seems we constantly produce new fat cells irrespective of our body weight status, sex or age.

"The total number of fat cells in the body is stable over time, because the making of new fat cells is counterbalanced by an equally rapid break down of the already existing fat cells due to cell death", says Prof Arner.

The study was made possible by a method to use radioactive isotopes in fat cells from people who had lived through the brief period of Cold War nuclear bomb testing from 1955 to 1963 to determine the age of the fat cells in the body.

This was combined with methods to carefully measure the size of the fat cells in relation to the total amount of adipose tissue in 687 people with a large individual variation in body weight who had undergone liposuction and abdominal reconstruction surgery.

Fat cells are replaced at the same rate that they die - roughly 10 per cent every year. The level of obesity is determined by a combination of the number and size of fat cells, which can grow or shrink as fat from food is deposited in them.

Even if obese subjects go on a diet they keep the total number of fat cells in the body constant, but the size of individual fat cells is decreased markedly.

The findings therefore provide a new target for treatment of obesity, namely by attacking the signals and genes in fat cells that control the formation of new such cells.

"The results may, at least in part, explain why it is so difficult to maintain the weight after slimming", adds Prof Arner.

"Until now it was not clear whether there was fat cell turnover in adults," adds Dr Spalding. "Now we have established this does occur, we can target the process.

"Various groups are looking at compounds that might regulate the formation of fat cells but this work is at too early a stage to say when anti obesitiy drugs based on this understanding will be tested on patients, if at all."

Other new insights into how to treat obesity could come from the gene sequence linked to an expanding waist line, weight gain and a tendency to develop type 2 diabetes in the Imperial led study.

Professor Jaspal Kooner, the paper's senior author from the National Heart and Lung Institute at Imperial College London, says: "Finding such a close association between a genetic sequence and significant physical effects is very important, especially when the sequence is found in half the population."

The study shows that the sequence is a third more common in those with Indian Asian than in those with European ancestry. This could provide a possible genetic explanation for the particularly high levels of obesity and insulin resistance in Indian Asians, who make up 25 per cent of the world's population, but who are expected to account for 40 per cent of global heart disease by 2020.

The new gene sequence sits close to a gene called MC4R, which regulates energy levels in the body by influencing how much we eat and how much energy we expend or conserve. The researchers believe the sequence is involved in controlling the MC4R gene, which has also been implicated in rare forms of extreme childhood obesity.

Previous research on finding the genetic causes of obesity has identified other energy-conserving genes. Combining knowledge about the effects of all these genes could pave the way for transforming how obesity is managed.

This research, backed by the British Heart Foundation, was carried out with scientists from the University of Michigan and the Pasteur Institute, France.

Last year a British led team found that if people carry one copy of a variant in a gene called FTO, as does half of the general population, it will lead to a gain in weight of 2.6lb or put just over half an inch on their waists and raise their risk of being obese by one third.

If people have two copies of this variant in the FTO gene, which is the case in one in six of the population, then they will gain almost 7lb more than those who lack the variation and are at a 70 per cent higher risk of obesity.

According to the 2001 Health Survey for England, more than a fifth of males and a similar proportion of females aged 16 and over were classified as obese.